Becoming pregnant: exploring the perspectives of women living with diabetes

Background The risk of adverse pregnancy outcome for women with type 1 diabetes is reduced through tight diabetes control. Most women enter pregnancy with inadequate blood glucose control. Interview studies with women suggest the concept of ‘planned’ and ‘unplanned’ pregnancies is unhelpful. Aim To explore women's accounts of their journeys to becoming pregnant while living with type 1 diabetes. Design of study Semi-structured interviews with 15 women living with pre-gestational type 1 diabetes, between 20 and 30 weeks gestation and with a normal pregnancy ultrasound scan. Setting Four UK specialist diabetes antenatal clinics. Method Interviews explored women's journeys to becoming pregnant and the impact of health care. Analysis involved comparison of women's accounts of each pregnancy and a thematic analysis. Results Women's experiences of becoming pregnant were diverse. Of the 40 pregnancies described, at least one positive step towards becoming pregnant was taken by 11 women in 23 pregnancies but not in the remaining 17 pregnancies, with variation between pregnancies. Prior to and in early pregnancy, some women described themselves as experts in their diabetes but most described seeking and/or receiving advice from their usual health professionals. Three women described pre-conception counselling and the anxiety this provoked. Conclusion For women living with type 1 diabetes each pregnancy is different. The concept of planned and unplanned pregnancy is unhelpful for designing health care. Formal preconception counselling can have unintended consequences. Those providing usual care to women are well positioned to provide advice and support to women about becoming pregnant, tailoring it to the changing needs and situation of each woman.

I got pregnant, I was so like ... crying inside...: experiences of women of Pakistani ancestry seeking contraception in the UK

South Asian women in Britain are less likely to use contraception than women in other ethnic groups. Previous studies have identified a lack of knowledge combined with low levels of English language and/or literacy as barriers to using contraception, but have not examined in detail women's experiences of accessing services. This qualitative study focused on the experiences of 19 Muslim women of Pakistani ancestry and the views of six health and community workers. The findings detail considerable institutional barriers to accessing contraceptive services, such as a lack of information and the paternalistic attitudes of some health professionals. The study suggests that, although all the women were motivated to access and use contraception, their ability to make informed choices was often limited. It was only when the women encountered advocates, who might be professionals or from their social networks, that they could begin to take control of their fertility. This study is consistent with earlier research and shows that lack of access to contraceptive services can have high personal and social costs for South Asian women.

Advocating alcohol abstinence to pregnant women: some observations about British policy

In 2007, the English Department of Health (DH) issued advice stating 'pregnant woman' and 'those trying to conceive' should abstain from drinking alcohol. As others have noted, this advice was issued despite their being no new evidence about the deleterious effects of low levels of alcohol consumption. In this paper, we argue this development is significant for the social construction of 'risk', since in advocating abstinence without an evidence base for this advice, policy makers formalise a connection between uncertainty and danger. We suggest this development has important implications, most obviously for pregnant women, certainly impacting on the nature of the advice they will now receive and likely more generally on their experience of the transition to motherhood. We suggest it has wider implications for individuals' experience also, as policy makers appear to be advocating the same approach to risk to non-pregnant people. Further, it suggests a noteworthy formalisation of a new definition of risk, which should be debated far more extensively, as it matters for the future development of health policy.

Retinal thickness in pregnant women with diabetes

Poster section Design. Retrospective study. Purpose. To assess whether there are changes in foveal thickness (FT) and total macular volume (TMV) in pregnancy in diabetic subjects. Methods. The audit consisted of pregnant women with diabetes, with no maculopathy, who completed their antenatal care at Birmingham Heartlands Hospital. The Zeiss Stratus Optical coherence tomography (OCT) was performed on patients attending diabetic retinopathy (DR) screening at intervals throughout their pregnancy. To be included in the audit patients had to have at least one OCT scan during their pregnancy. Results. Altogether there were 8 type 1 and 22 type 2 patients with mean diabetes duration of 6 years (range 1-20). Mean gestation at DR screening with OCT during the first trimester was 9.7 weeks (6-13) (n=22). The mean and standard deviation for FT for the right was 179.1 µm ± 21.49 and for the left eye was 187.3 µm ± 23.55. The mean TMV was right 6.43 µm ± 0.35 and left 6.50 µm ± 0.39. The mean gestation at DR screening with OCT during the second trimester was 23.4 weeks (18-26) (n=25). The mean FT for the right was 191.4 µm ± 22.70 and the left 195.6 µm ± 24.77. The mean TMV was right 6.74 µm ± 0.45 and left 6.91 µm ± 0.35. The gestation of DR screening with OCT during the third trimester was 31.1 weeks (27-36) (n=15). The mean FT for the right was 181.5 µm ± 24.84 and for the left 193.1 µm ± 28.55. The mean TMV was right 6.80 µm ± 0.40 and left 6.84 µm ± 0.31. There were no significant differences in FT over the 3 trimesters. The TMV showed a significant difference when comparing the first and second trimesters (p<0.05). However, there was no significant statistical difference in TMV in the second and third trimesters. None of the patients showed any macula edema on the OCT. Conclusions. The results suggest there is no significant change in foveal thickness in pregnancy in diabetic subjects. There was a significant statistical difference in total macular volume in the second trimester; however, this would not be clinically significant. This is an important observation proven by the OCT which has not been previously studied.

Heparin elevates circulating soluble fms-like tyrosine kinase-1 immunoreactivity in pregnant women receiving anticoagulation therapy

Background—Alterations in circulating levels of pro- and antiangiogenic factors have been associated with adverse pregnancy outcomes. Heparin is routinely administered to pregnant women, but without clear knowledge of its impact on these factors. Methods and Results—We conducted a longitudinal study of 42 pregnant women. Twenty-one women received prophylactic heparin anticoagulation, and 21 healthy pregnant women served as controls. Compared with gestational age-matched controls, heparin treatment was associated with increased circulating levels of soluble fms-like tyrosine kinase-1 (sFlt-1) in the third trimester (P<0.05), in the absence of preeclampsia, placental abruption, or fetal growth restriction. Heparin had no effect on circulating levels of vascular endothelial growth factor, placenta growth factor, or soluble endoglin as assessed by ELISA. In vitro, low-molecular weight and unfractionated heparins stimulated sFlt-1 release from placental villous explants, in a dose- and time-dependent manner. This effect was not due to placental apoptosis, necrosis, alteration in protein secretion, or increased transcription. Western blot analysis demonstrated that heparin induced shedding of the N-terminus of Flt-1 both in vivo and in vitro as indicated by a predominant band of 100–112 kDa. By using an in vitro angiogenesis assay, we demonstrated that serum of heparin-treated cases inhibited both basal and vascular endothelial growth factor-induced capillary-like tube formation. Conclusions—Heparin likely increases the maternal sFlt-1 through shedding of the extracellular domain of Flt-1 receptor. Our results imply that upregulation of circulating sFlt-1 immunoreactivity in pregnancy is not always associated with adverse outcomes, and that heparin's protective effects, if any, cannot be explained by promotion of angiogenesis.

Autoantibody from women with preeclampsia induces soluble Fms-like tyrosine kinase-1 production via angiotensin type 1 receptor and calcineurin/nuclear factor of activated T-cells signaling

Preeclampsia is a pregnancy-specific hypertensive syndrome that causes substantial maternal and fetal morbidity and mortality. Recent evidence indicates that maternal endothelial dysfunction in preeclampsia results from increased soluble Fms-like tyrosine kinase-1 (sFlt-1), a circulating antiangiogenic protein. Factors responsible for excessive production of sFlt-1 in preeclampsia have not been identified. We tested the hypothesis that angiotensin II type 1 (AT1) receptor activating autoantibodies, which occur in women with preeclampsia, contribute to increased production of sFlt-1. IgG from women with preeclampsia stimulates the synthesis and secretion of sFlt-1 via AT1 receptor activation in pregnant mice, human placental villous explants, and human trophoblast cells. Using FK506 or short-interfering RNA targeted to the calcineurin catalytic subunit mRNA, we determined that calcineurin/nuclear factor of activated T-cells signaling functions downstream of the AT1 receptor to induce sFlt-1 synthesis and secretion by AT1-receptor activating autoantibodies. AT1-receptor activating autoantibody–induced sFlt-1 secretion resulted in inhibition of endothelial cell migration and capillary tube formation in vitro. Overall, our studies demonstrate that an autoantibody from women with preeclampsia induces sFlt-1 production via angiotensin receptor activation and downstream calcineurin/nuclear factor of activated T-cells signaling. These autoantibodies represent potentially important targets for diagnosis and therapeutic intervention.

Pregnancy complications in hyperemesis-affected pregnancy:a large hospital database study

Objective: Vomiting in pregnancy is a common condition affecting 80% of pregnant women. Hyperemesis is at one end of the spectrum, seen in 0.5–2% of the pregnant population. Known factors such as nulliparity, younger age and high body mass indexare associated with an increased risk of this condition in the first trimester. Late pregnancy complications attributable to hyperemesis, the pathogenesis of which is poorly understood, have not been studied in large population-based studies in the United Kingdom. The objective of this study was to determine a plausible association between hyperemesis and pregnancy complications,such as pregnancy-related hypertension, gestational diabetes and liver problems in pregnancy, and the rates of elective (ElCS) and emergency caesarean section (EmCS). Methods: Using a database based on ICD-10 classification, anonymised data of admissions to a large multi-ethnic hospital in Manchester, UK between 2000 and 2012 were examined.Notwithstanding the obvious limitations with hospital database-based research, this large volume of datasets allows powerful studies of disease trends and complications.Results Between 2000 and 2012, 156 507 women aged 45 or under were admitted to hospital. Of these, 1111 women were coded for hyperemesis (0.4%). A greater proportion of women with hyperemesis than without hyperemesis were coded forhypertensive disorders in pregnancy such as pregnancy-induced hypertension, pre-eclampsia and eclampsia (2.7% vs 1.5%;P=0.001). The proportion of gestational diabetes and liver disorders in pregnancy was similar for both groups (diabetes:0.5% vs. 0.4%; P=0.945, liver disorders: 0.2% vs. 0.1%;P=0.662). Hyperemesis patients had a higher proportion of elective and emergency caesarean sections compared with the non-hyperemesis group (ElCS: 3.3% vs. 2%; P=0.002, EmCS: 5% vs.3%; P=0.00). Conclusions: There was a higher rate of emergency and elective caesarean section in women with hyperemesis, which could reflect the higher prevalence of pregnancy-related hypertensive disorders(but not diabetes or liver disorders) in this group. The factors contributing to the higher prevalence of hypertensive disorders arenot known, but these findings lead us to question whether there is a similar pathogenesis in the development of both the conditions and hence whether further study in this area is warranted.

Hydrogen sulphide rescues preeclampsia-like phenotype aggravated by high sFlt-1 in placenta growth factor (PlGF) deficiency

Placenta growth factor (PlGF) deficient mice are fertile at a Mendelian ratio. Interestingly, low maternal plasma levels of PlGF are strongly associated with early onset of preeclampsia, a pregnancy hypertensive disorder characterised by high blood pressure, proteinuria and fetal growth restriction. PlGF is increasingly being recognised as an early diagnostic biomarker, but the physiological importance of PlGF in the pathogenesis of preeclampsia is unknown. We investigated whether the decreased levels of PlGF in pregnancy exacerbate the fetal growth restriction associated with preeclampsia in the presence of high sFlt-1 and the potential of hydrogen sulphide to ameliorate these effects. Pregnant PlGF−/− mice were injected with adenovirus encoding sFlt-1 (Ad-sFlt-1) at 1 × 109 pfu/ml at E10.5 and mean arterial blood pressure (MAP), biochemical and histological analysis of maternal kidney, placenta and embryos were assessed at the end of pregnancy. Ad-sFlt-1 significantly increased MAP and induced severe glomerular endotheliosis in PlGF−/− mice compared to wild-type animals. Soluble Flt-1 also significantly elevated albumin–creatinine ratio and increased levels of urinary kidney injury molecule-1, a marker for proximal tubule injury. Furthermore, sFlt-1 over expression increased fetal resorption rate in the PlGF−/− mice and promoted abnormal placental vascularisation. To determine whether placental PlGF is critical for preventing fetal growth restriction associated with preeclampsia, we generated haploinsufficient PlGF+/− placentas and embryos in dams and exposed to high sFlt-1 environment. These mothers showed reduced fetal resorption, gestational hypertension and proteinuria when compared to pregnant PlGF−/− mice. Furthermore, treatment with hydrogen sulphide-releasing agent, GYY4137, significantly reduced resorption, hypertension and proteinuria observed in Ad-sFlt-1 treated pregnant PlGF−/− mice. Our study shows that placental PlGF is a critical protective factor against the damaging effects of high sFlt-1 associated with preeclampsia and activation of the hydrogen sulphide pathway may rescue preeclampsia phenotypes even under low PlGF environment.

Hydrogen sulphide rescues preeclampsia-like phenotype aggravated by high sFlt-1 in Placenta Growth Factor (PlGF) deficiency

INTRODUCTION: Low circulating levels of placenta growth factor (PlGF) is strongly associated with the onset of preeclampsia, a maternal hypertensive disorder characterized by high blood pressure and proteinuria after 20 weeks of gestation. Although, PlGF-deficient mice are born healthy and fertile at a Mendelian ratio, the physiological importance of PlGF in the pathogenesis of preeclampsia is unclear. We hypothesised that decreased levels of PlGF in pregnancy exacerbates the fetal growth restriction associated with preeclampsia in the presence of high sFlt-1. METHODS: Pregnant PlGF-/- mice were injected with adenovirus encoding sFlt-1 (Ad-sFlt-1) at high (i) 1.5x109 pfu/ml and low (ii) 0.5x109 pfu/ml doses. Mean arterial blood pressure (MBP), biochemical and histological assessments of maternal kidney, placenta and embryos were performed. RESULTS: Ad-sFlt-1 significantly increased MBP and induced severe glomerular endotheliosis in PlGF-/- mice at E10.5 gestation compared to wild-type animals. High sFlt-1 also significantly elevated albumincreatinine ratio and increased levels of urinary kidney injury molecule-1, a marker for proximal tubule injury.At a high dose of sFlt-1, there was complete fetal resorption in the pregnant PlGF-/- mice, and even the lower dose of sFlt-1 induced severe fetal resorption and abnormal placental vascularization. Hydrogen sulphide-releasing agent, GYY4137, significantly reduced resorption, hypertension and proteinuria in Ad-sFlt-1 treated pregnant PlGF-/- mice. To determine if placental PlGF is critical for preventing fetal growth restriction associated with preeclampsia, we generated haploinsufficient PlGF+/- placentas and embryos were generated in wild-time dams and exposed to high sFlt-1 environment. This resulted in reduced fetal resorption, gestational hypertension and proteinuria when compared to pregnant PlGF-/- mice. CONCLUSIONS: Placental PlGF is a critical protective factor against the damaging effects of high sFlt-1 in preeclampsia and the hydrogen sulphide pathway may rescue preeclampsia phenotypes.